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The product shown in Figure 8.1 was used to prepare an IV bag containing 600 mg/50 mL of injectable solution. How many milliliters of this solution should be given for each divided dose?
CASE IN POINT 8.2
A pediatric patient is being administered enalaprilat every 12 hours by intravenous injection to manage hypertension and possible heart
failure.4 Based on a dose of 5 mcg/kg, the patient is receiving 55 mcg of enalaprilat per dose. The physician wishes to convert the patient to oral enalapril at a dosage of 100 mcg/kg as a single daily dose. The standard procedure is to crush a 2.5-mg tablet of enalapril, mix with sterile water to make 12.5 mL, and administer the appropriate dose using a calibrated oral dispenser. Calculate the dose, in milliliters, to be administered to this patient.
FIGURE 8.1 Product label showing the drug concentration in mg/mL for an injectable product. (Source:
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm? setid=d157983f-4794-400d-a3cf-c515d0c24b62. Courtesy of
Pfizer, Inc.)
Geriatric Patients
Although the term elderly is subject to varying definitions with regard to chronologic age, it is clear that the functional capacities of most organ systems decline throughout adulthood, and important changes in drug response occur with advancing age. Geriatric medicine or geriatrics is the field that encompasses the management of illness in the elderly.
In addition to medical conditions affecting all age groups, some conditions are particularly common in the elderly, including degenerative osteoarthritis, congestive heart failure, venous and arterial insufficiency, stroke, urinary incontinence, prostatic carcinoma, parkinsonism, and
Alzheimer’s disease. Many elderly patients have coexisting pathologies that require multiple-drug therapies.
Most age-related physiologic functions peak before age 30, with subsequent gradual linear decline.6 Reductions in physiologic capacity
and function are cumulative, becoming more profound with age. Kidney function is a major consideration in drug dosing in the elderly because reduced function results in reduced drug elimination.
Because reduced kidney function increases the possibility of toxic drug levels in the body and adverse drug effects, initial drug dosing in the elderly patient often reflects a downward variance from the usual adult dose. There is also a frequent need for dosage adjustment or medication change due to adverse effects or otherwise unsatisfactory therapeutic outcomes.
There are a number of other common features of medication use in the elderly, including the long-term use of maintenance drugs; the need for multidrug therapy, with the attendant increased possibility of drug interactions and adverse drug effects; and difficulties in patient adherence. The latter is often due to impaired cognition, confusion over the various dosing schedules of multiple medications, and economic reasons in not being able to afford the prescribed medication.
Special considerations in dose determinations for elderly patients
Dose determinations for elderly patients frequently require consideration of some or all of the following:
Therapy is often initiated with a lower-than-usual adult dose. Dose adjustment may be required based on the therapeutic response. The patient’s physical condition may determine the drug dose and the route of administration used. The dose may be determined, in part, on the patient’s weight, body surface area, health and disease status, and pharmacokinetic factors. Concomitant drug therapy may affect drug/dose effectiveness. A drug’s dose may produce undesired adverse effects and may affect patient adherence. Complex dosage regimens of multiple drug therapy may affect patient adherence.
The adult dose of a drug is 500 mg every 8 hours. For an elderly patient with impaired renal function, the dose is reduced to 250 mg every 6 hours. Calculate the reduction in the daily dose, in milligrams.
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Dosage Forms Applicable to Pediatric and Geriatric Patients
In the general population, solid dosage forms, such as tablets and capsules, are preferred for the oral administration of drugs because of their convenience, precise dose, ease of administration, ready identification, transportation, and lower cost per dose relative to other dosage forms. However, solid dosage forms are often difficult or impossible for the pediatric, geriatric, or infirm patient to swallow. In these instances, liquid forms are preferred, such as oral solutions, syrups, suspensions, and drops. With liquid forms, the dose can be adjusted by changing the volume administered. When necessary, liquid forms of medication may be administered by oral feeding tube. Pharmacists are sometimes asked to compound an oral liquid from a counterpart solid dosage form when a liquid product is not available. Chewable tablets and solid gel forms (medicated “gummy bears”) that disintegrate or dissolve in the mouth are often used for pediatric and geriatric patients. In addition, and as noted in Chapter 7, tablet splitting and tablet crushing are options for individuals unable to swallow whole tablets.
For systemic effects, injections may be used rather than the oral route of administration when needed for pediatric and elderly patients, with the dose or strength of the preparation adjusted to meet the requirements of the individual patient.
Drug Dosage Based on Age
For reasons stated earlier, the young and the elderly require special dosing considerations based on factors characteristic of these groups.
Before the physiologic differences between adult and pediatric patients were clarified, the latter were treated with drugs as if they were merely miniature adults. Various rules of dosage in which the pediatric dose was a fraction of the adult dose, based on relative age, were created for youngsters (e.g., Young’s rule). Today these rules are not in general
use because age alone is no longer considered a singularly valid criterion in the determination of accurate dosage for a child, especially when calculated from the usual adult dose, which itself provides wide
clinical variations in response. Some of these rules are presented in the footnote for perspective and historical purposes.
a
a
Young’s rule, based on age:
NOTE: The value of 150 in Fried’s rule was an estimate of the age (12.5 years or 150 months) of an individual who would normally receive an adult dose, and the number 150 in Clark’s rule was an estimate of the weight of an individual who likewise would receive an adult dose.
Currently, when age is considered in determining dosage of a potent therapeutic agent, it is used generally in conjunction with another factor, such as weight. This is exemplified in Table 8.1, in which the dose of the drug digoxin is determined by a combination of the patient’s age and weight.
TABLE 8.1 ILLUSTRATIVE PEDIATRIC DOSAGES OF
DIGOXIN BASED ON AGE AND WEIGHT
ª
a
These are estimated oral maintenance doses for patients with normal renal function. Specific pediatric doses for various clinical conditions and by various routes of administration may be found at Facts & Comparisons eAnswers [book online]. Baltimore, MD: Wolters Kluwer Clinical Drug Information Inc.; 2020.
Example calculations of dose based on age
1. An over-the-counter cough remedy contains 120 mg of
dextromethorphan in a 60-mL bottle of product. The label states the
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dose as 1½ teaspoonfuls for a child 6 years of age. How many milligrams of dextromethorphan are contained in the child’s dose?
2. The dose of a drug for a child is acceptable as either 10 mg/kg or 300
mg. Calculate the difference in these alternative doses for a 9-year­old child weighing 70 lb.
Dose at 10 mg/kg: 70 lb ÷ 2.2 lb/kg = 31.82 kg; 31.82 kg × 10 mg/kg = 318.18 mg Difference in dose = 318.18 mg − 300 mg = 18.18 mg
3. From the data in Table 8.1, calculate the dosage range for digoxin for
a 20-month-old infant weighing 6.8 kg.
Dosage range between 38.08 and 63.92 mcg digoxin administered twice daily
Drug Dosage Based on Body Weight
Drug doses based on weight are expressed as a specific quantity of drug per unit of patient weight, such as milligrams of drug per kilogram of body weight (abbreviated [mg/kg]). Dosing in this manner makes the quantity of drug administered specific to the weight of the patient being treated.
Example calculations of dose based on body weight
A useful equation for the calculation of dose based on body weight is:
This equation is based on a drug dose in mg/kg and the patient’s weight in kilograms. When different units are given or desired, other units may be substituted in the equation as long as the terms used are consistently applied.
1. The usual initial dose of chlorambucil is 150 mcg/kg of body weight.
How many milligrams should be administered to a person weighing 154 lb?
Solving by the equation: 150 mcg = 0.15 mg and 1 kg = 2.2 lb Or, solving by ratio and proportion: 150 mcg = 0.15 mg and 1 kg = 2.2 lb Or, solving by dimensional analysis:
2. The usual dose of trimethoprim for infants over 6 months of age and
children is 5 mg/kg administered every 12 hours. What would be the daily dose for a child weighing 44 lb?
3. The dose of extended-release minocycline to treat acne vulgaris is given as 1 mg/kg/day × 12 weeks. Tablet strengths available include 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, and 115 mg of minocycline. What strength tablet and how many tablets should be prescribed for the entire course of treatment for a 100-lb patient?
4. A dose of enoxaparin sodium injection (LOVENOX) is “1 mg/kg q12h SC.” If a graduated prefilled syringe containing 80 mg/0.8 mL is used, how many milliliters should be administered per dose to a 154­lb patient?
CASE IN POINT 8.3
A hospital pharmacist is called to a pediatric nursing station to calculate the quantity of an injection to administer to a pediatric patient. The daily dose of the injection for the child’s weight is stated as 15 mg/kg/day, divided into three equal portions. The child weighs 10 kg. The injection contains 5 mg/mL of the prescribed drug. How many milliliters of injection should be administered?
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Dosing tables based on body weight
For some drugs dosed according to body weight or body surface area, dosing tables appear in product literature to assist the physician and pharmacist. An example is presented in Table 8.2.
TABLE 8.2 DOSING BY BODY WEIGHT FOR A HYPOTHETICAL DRUG
1. Using Table 8.2 and a daily dose of 0.5 mg/kg, how many 20-mg capsules of the drug product should be dispensed to a patient weighing 176 lb if the dosage regimen calls for 15 weeks of therapy?
According to table 8.2, the patient should receive 40 mg/day, or two 20-mg capsules/day 2 capsules/day × 7 days/week × 15 weeks = 210 capsules
2. A pharmacist compounds a suspension from oseltamivir phosphate
capsules to contain 15 mg of drug per milliliter. Using Table 8.3, calculate the single dose in milliliters for a pediatric patient weighing 40 lb.
From Table 8.3, the dose for the pediatric patient is 45 mg twice daily.
TABLE 8.3 DOSING OF OSELTAMIVIR PHOSPHATE IN THE TREATMENT OF INFLUENZA IN PEDIATRIC
PATIENTS
a
a
Adapted from product literature for oseltamivir phosphate (TAMIFLU); Genentech, 2014. Available at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021087s071,021246s054lbl.pdf
Drug Dosage Based on Body Surface Area
Body surface area (BSA) of a patient is determined based on height and weight as discussed in following sections. The BSA method of calculating drug doses is widely used for two types of patient groups: cancer patients receiving chemotherapy and pediatric patients.
Example calculations of dose based on body surface area
A useful equation for the calculation of dose based on BSA is:
If the adult dose of a drug is 100 mg, calculate the approximate dose
for a child with a BSA of 0.83 m2.
Dosing tables based on body surface area
For certain drugs, dosing tables may be provided to determine the approximate dose based on a patient’s body surface area. Table 8.4 presents an example for a hypothetical drug.
TABLE 8.4 PEDIATRIC DOSING GUIDELINE FOR A
HYPOTHETICAL DRUG BASED ON BSA
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Using Table 8.4, find the dose of the hypothetical drug at a dose level of 300 mg/m2 for a child determined to have a BSA of 1.25 m2. Calculate to
verify.
From Table 8.4, the dose is 375 mg From calculations, the dose is 300 mg/m2 × 1.25 m2 = 375 mg
Nomograms for determining body surface area
Most BSA calculations use a standard nomogram, which includes both weight and height. Nomograms for children and adults are shown in
Figures 8.2 and 8.3. The BSA of an individual is determined by drawing
a straight line connecting the person’s height and weight. The point at which the line intersects the center column indicates the person’s BSA in square meters. In the example shown in Figure 8.2, a child weighing 15
kg and measuring 100 cm in height has a BSA of 0.64 m2.
FIGURE 8.2 Body surface area of children. (Reprinted with permission from Diem K, Lentner C, Geigy JR. Scientific Tables. 7th Ed. Basel, Switzerland: Ciba-Geigy; 1970:538. Copyright © Novartis AG.)
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